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Identification of critical variants within SLC44A4, an ulcerative colitis susceptibility gene identified in a GWAS in north Indians

Genes & Immunity volume 17, pages 105–109 (2016)Cite this article

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Abstract

SLC44A4 is one of the seven novel susceptibility genes that were discovered in the first ever genome-wide association study (GWAS) on ulcerative colitis (UC) in the genetically distinct north Indians. This gene seems to be functionally relevant to disease biology as it may contribute to the associated phenotype of Vitamin B1 deficiency among UC patients, hence playing a role in disease pathogenesis. A large number of single-nucleotide polymorphisms (SNPs) are known to be distributed throughout this gene, but the functional status of most are not known. Thus, an extensive investigation of structural and regulatory variants within this gene was undertaken in this study to identify the critical variants amongst them using a combination of fine mapping, in silico and in vitro approaches. A few intronic SNPs were predicted to have regulatory roles on the basis of in silico analysis, suggesting that they may be the critical variants within SLC44A4. This highlights the importance of this gene in UC biology, thus confirming the finding of the GWAS and also warranting additional studies.

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Acknowledgements

We thank our clinical collaborators Professor Ajit Sood and Dr. Vandana Midha from Dayanand Medical College and Hospital, Ludhiana, Punjab, for providing blood samples from UC patients. We thank Ms. Anjali Dhyani for preparation of DNA samples and maintenance of the resource in the lab. We thank Central Instrumentation Facility, University of Delhi South Campus, New Delhi, for DNA sequencing services. We acknowledge financial support through the Centre of Excellence in Genome sciences and predictive medicine - Functional characterization of SNPs/SNP haplotypes in candidate genes (BT/01/COE/07/UDSC/2008) from the Department of Biotechnology, Government of India to BKT Junior and senior research fellowship to AG from Council of Scientific and Industrial Research, New Delhi, is gratefully acknowledged. We acknowledge the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) for the Immunochip genotyping data for UC patients and controls from north India. Infrastructure support provided to the Department of Genetics, UDSC, by the University Grants Commission, New Delhi, under the Special Assistance Programme and Department of Science and Technology, New Delhi, under FIST and DU-DST PURSE programmes is gratefully acknowledged.

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  1. Department of Genetics, University of Delhi South Campus, New Delhi, India

    A Gupta & B K Thelma

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  1. A Gupta
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Correspondence to B K Thelma.

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Gupta, A., Thelma, B. Identification of critical variants within SLC44A4, an ulcerative colitis susceptibility gene identified in a GWAS in north Indians. Genes Immun 17, 105–109 (2016). https://doi.org/10.1038/gene.2015.53

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